-
Fertility and Sterility Jan 2020To synthesize evidence on the most effective pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy. (Meta-Analysis)
Meta-Analysis
Perioperative nonhormonal pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy: a systematic review and network meta-analysis.
OBJECTIVE
To synthesize evidence on the most effective pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy.
DESIGN
Systematic review and network meta-analysis of randomized controlled trials (RCTs).
SETTING
Not applicable.
PATIENTS
Trials assessing efficacy of pharmacological interventions during different types of myomectomy.
INTERVENTIONS
Misoprostol, oxytocin, vasopressin, tranexamic acid (TXA), epinephrine, or ascorbic acid.
MAIN OUTCOME MEASURES
Intraoperative blood loss and need for blood transfusion.
RESULTS
The present review included 26 randomized control trials (RCTs) (N = 1627). For minimally invasive procedures (9 RCTs; 474 patients), network meta-analysis showed that oxytocin (mean difference [MD] -175.5 mL, 95% confidence interval [CI] -30.1.07, -49.93), ornipressin (MD -149.6 mL, 95% CI - 178.22, -120.98), misoprostol, bupivacaine plus epinephrine, and vasopressin were effective in reducing myomectomy blood loss, but the evidence is of low quality. Ranking score of treatments included in subgroup analysis of minimally invasive myomectomy showed that oxytocin ranked first in reducing blood loss, followed by ornipressin. For open myomectomy (17 RCTs; 1,153 patients), network meta-analysis showed that vasopressin plus misoprostol (MD -652.97 mL, 95% CI - 1113.69, -174.26), oxytocin, TXA, and misoprostol were effective; however, the evidence is of low quality. Vasopressin plus misoprostol ranked first in reducing blood loss during open myomectomy (P = .97).
CONCLUSION
There is low-quality evidence to support uterotonics, especially oxytocin, and peripheral vasoconstrictors as effective options in reducing blood loss and need for blood transfusion during minimally invasive myomectomy. Oxytocin is the most effective intervention in minimally invasive myomectomy. For open myomectomy, a combination of uterotonics and peripheral vasoconstrictors is needed to effectively reduce blood loss.
Topics: Blood Loss, Surgical; Female; Humans; Leiomyoma; Minimally Invasive Surgical Procedures; Network Meta-Analysis; Oxytocin; Perioperative Care; Randomized Controlled Trials as Topic; Uterine Myomectomy; Uterine Neoplasms
PubMed: 31753311
DOI: 10.1016/j.fertnstert.2019.09.016 -
Neuroscience and Biobehavioral Reviews Jan 2020Oxytocin (OT) subserves various physiological, behavioral, and cognitive processes. This paired with the ability to administer OT with minimal and inconsistent side...
Oxytocin (OT) subserves various physiological, behavioral, and cognitive processes. This paired with the ability to administer OT with minimal and inconsistent side effects has spurred research to explore its therapeutic potential. Findings from single-dose studies indicate that OT administration may be beneficial, at least under certain circumstances. The state of the field, however, is less clear regarding effects from chronic OT administration, which more closely resembles long-term treatment. To address this gap, this review synthesizes existing findings on the use of chronic OT administration in animal and human work. In addition to detailing the effects of chronic OT administration across different functional domains, this review highlights factors that have contributed to mixed findings. Based on this review, a basic framework of interrelated regulatory functions sensitive to chronic OT administration is offered. The paper also identifies future research directions across different contexts, populations, and outcomes, specifically calling for more systematic and standardized research on chronic OT administration in humans to supplement and expand what is currently known from preclinical work.
Topics: Animals; Anxiety; Autism Spectrum Disorder; Dementia; Humans; Inflammation; Oxytocin; Pain; Schizophrenia; Sexual Dysfunction, Physiological; Stress Disorders, Post-Traumatic; Stress, Psychological; Substance-Related Disorders
PubMed: 31647964
DOI: 10.1016/j.neubiorev.2019.10.012 -
Revista Latino-americana de Enfermagem Aug 2019to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor.
OBJECTIVE
to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor.
METHOD
systematic review with database searches. First, two researchers independently selected the papers and, at a second point in time, held a reconciliation meeting. The Kappa coefficient was used to assess agreement, while the Grading of Recommendations, Assessment, Development and Evaluation was adopted to assess risk of bias and classify level of evidence.
RESULTS
in this review, 42 papers were included, 34 of which addressed product technologies, most referred to pharmacological products, while two papers addressed the use of blood transparent plastic bags collector and the contribution of birth spacing and prenatal care. The eight papers addressing process technologies included the active management of the third stage of labor, controlled cord traction, uterine massage, and educational interventions.
CONCLUSION
product and process technologies presented high and moderate evidence confirmed in 61.90% of the papers. The levels of evidence confirm the contribution of technologies to prevent and control hemorrhaging. Clinical nurses should provide scientific-based care and develop protocols addressing nursing care actions.
Topics: Bias; Biomedical Technology; Female; Humans; Labor Stage, Third; Misoprostol; Oxytocics; Postpartum Hemorrhage; Pregnancy; Risk Factors
PubMed: 31432919
DOI: 10.1590/1518-8345.2761.3165 -
BMC Pregnancy and Childbirth Aug 2019Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a...
BACKGROUND
Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies.
METHODS
An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects.
RESULTS
Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin.
CONCLUSIONS
Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does.
Topics: Female; Humans; Labor, Obstetric; Oxytocics; Oxytocin; Parturition; Pregnancy
PubMed: 31399062
DOI: 10.1186/s12884-019-2365-9 -
The Cochrane Database of Systematic... Jun 2019In most pregnancies that miscarry, arrest of embryonic or fetal development occurs some time (often weeks) before the miscarriage occurs. Ultrasound examination can...
BACKGROUND
In most pregnancies that miscarry, arrest of embryonic or fetal development occurs some time (often weeks) before the miscarriage occurs. Ultrasound examination can reveal abnormal findings during this phase by demonstrating anembryonic pregnancies or embryonic or fetal death. Treatment has traditionally been surgical but medical treatments may be effective, safe, and acceptable, as may be waiting for spontaneous miscarriage. This is an update of a review first published in 2006.
OBJECTIVES
To assess, from clinical trials, the effectiveness and safety of different medical treatments for the termination of non-viable pregnancies.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (24 October 2018) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials comparing medical treatment with another treatment (e.g. surgical evacuation), or placebo, or no treatment for early pregnancy failure. Quasi-randomised studies were excluded. Cluster-randomised trials were eligible for inclusion, as were studies reported in abstract form, if sufficient information was available to assess eligibility.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
Forty-three studies (4966 women) were included. The main interventions examined were vaginal, sublingual, oral and buccal misoprostol, mifepristone and vaginal gemeprost. These were compared with surgical management, expectant management, placebo, or different types of medical interventions were compared with each other. The review includes a wide variety of different interventions which have been analysed across 23 different comparisons. Many of the comparisons consist of single studies. We limited the grading of the quality of evidence to two main comparisons: vaginal misoprostol versus placebo and vaginal misoprostol versus surgical evacuation of the uterus. Risk of bias varied widely among the included trials. The quality of the evidence varied between the different comparisons, but was mainly found to be very-low or low quality.Vaginal misoprostol versus placeboVaginal misoprostol may hasten miscarriage when compared with placebo: e.g. complete miscarriage (5 trials, 305 women, risk ratio (RR) 4.23, 95% confidence interval (CI) 3.01 to 5.94; low-quality evidence). No trial reported on pelvic infection rate for this comparison. Vaginal misoprostol made little difference to rates of nausea (2 trials, 88 women, RR 1.38, 95% CI 0.43 to 4.40; low-quality evidence), diarrhoea (2 trials, 88 women, RR 2.21, 95% CI 0.35 to 14.06; low-quality evidence) or to whether women were satisfied with the acceptability of the method (1 trial, 32 women, RR 1.17, 95% CI 0.83 to 1.64; low-quality evidence). It is uncertain whether vaginal misoprostol reduces blood loss (haemoglobin difference > 10 g/L) (1 trial, 50 women, RR 1.25, 95% CI 0.38 to 4.12; very-low quality) or pain (opiate use) (1 trial, 84 women, RR 5.00, 95% CI 0.25 to 101.11; very-low quality), because the quality of the evidence for these outcomes was found to be very low.Vaginal misoprostol versus surgical evacuation Vaginal misoprostol may be less effective in accomplishing a complete miscarriage compared to surgical management (6 trials, 943 women, average RR 0.40, 95% CI 0.32 to 0.50; Heterogeneity: Tau² = 0.03, I² = 46%; low-quality evidence) and may be associated with more nausea (1 trial, 154 women, RR 21.85, 95% CI 1.31 to 364.37; low-quality evidence) and diarrhoea (1 trial, 154 women, RR 40.85, 95% CI 2.52 to 662.57; low-quality evidence). There may be little or no difference between vaginal misoprostol and surgical evacuation for pelvic infection (1 trial, 618 women, RR 0.73, 95% CI 0.39 to 1.37; low-quality evidence), blood loss (post-treatment haematocrit (%) (1 trial, 50 women, mean difference (MD) 1.40%, 95% CI -3.51 to 0.71; low-quality evidence), pain relief (1 trial, 154 women, RR 1.42, 95% CI 0.82 to 2.46; low-quality evidence) or women's satisfaction/acceptability of method (1 trial, 45 women, RR 0.67, 95% CI 0.40 to 1.11; low-quality evidence).Other comparisonsBased on findings from a single trial, vaginal misoprostol was more effective at accomplishing complete miscarriage than expectant management (614 women, RR 1.25, 95% CI 1.09 to 1.45). There was little difference between vaginal misoprostol and sublingual misoprostol (5 trials, 513 women, average RR 0.84, 95% CI 0.61 to 1.16; Heterogeneity: Tau² = 0.10, I² = 871%; or between oral and vaginal misoprostol in terms of complete miscarriage at less than 13 weeks (4 trials, 418 women), average RR 0.68, 95% CI 0.45 to 1.03; Heterogeneity: Tau² = 0.13, I² = 90%). However, there was less abdominal pain with vaginal misoprostol in comparison to sublingual (3 trials, 392 women, RR 0.58, 95% CI 0.46 to 0.74). A single study (46 women) found mifepristone to be more effective than placebo: miscarriage complete by day five after treatment (46 women, RR 9.50, 95% CI 2.49 to 36.19). However the quality of this evidence is very low: there is a very serious risk of bias with signs of incomplete data and no proper intention-to-treat analysis in the included study; and serious imprecision with wide confidence intervals. Mifepristone did not appear to further hasten miscarriage when added to a misoprostol regimen (3 trials, 447 women, RR 1.18, 95% CI 0.95 to 1.47).
AUTHORS' CONCLUSIONS
Available evidence from randomised trials suggests that medical treatment with vaginal misoprostol may be an acceptable alternative to surgical evacuation or expectant management. In general, side effects of medical treatment were minor, consisting mainly of nausea and diarrhoea. There were no major differences in effectiveness between different routes of administration. Treatment satisfaction was addressed in only a few studies, in which the majority of women were satisfied with the received intervention. Since the quality of evidence is low or very low for several comparisons, mainly because they included only one or two (small) trials; further research is necessary to assess the effectiveness, safety and side effects, optimal route of administration and dose of different medical treatments for early fetal death.
Topics: Delivery, Obstetric; Female; Fetal Death; Humans; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic
PubMed: 31206170
DOI: 10.1002/14651858.CD002253.pub4 -
The Cochrane Database of Systematic... Apr 2019Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013.
OBJECTIVES
To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons.
AUTHORS' CONCLUSIONS
Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.
Topics: Blood Transfusion; Delivery, Obstetric; Female; Humans; Labor Stage, Third; Odds Ratio; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 31032882
DOI: 10.1002/14651858.CD001808.pub3 -
The Cochrane Database of Systematic... Feb 2019Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. This is an update of a review last published in 2015.
OBJECTIVES
To compare the effects of active versus expectant management of the third stage of labour on severe primary postpartum haemorrhage (PPH) and other maternal and infant outcomes.To compare the effects of variations in the packages of active and expectant management of the third stage of labour on severe primary PPH and other maternal and infant outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World health Organization International Clinical Trials Registry Platform (ICTRP), on 22 January 2018, and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Cluster-randomised trials were eligible for inclusion, but none were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, carried out data extraction and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included eight studies, involving analysis of data from 8892 women. The studies were all undertaken in hospitals, seven in higher-income countries and one in a lower-income country. Four studies compared active versus expectant management, and four compared active versus a mixture of managements. We used a random-effects model in the analyses because of clinical heterogeneity. Of the eight studies included, we considered three studies as having low risk of bias in the main aspects of sequence generation, allocation concealment and completeness of data collection. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.The evidence suggested that, for women at mixed levels of risk of bleeding, it is uncertain whether active management reduces the average risk of maternal severe primary PPH (more than 1000 mL) at time of birth (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, 3 studies, 4636 women, I = 60%; GRADE: very low quality). For incidence of maternal haemoglobin (Hb) less than 9 g/dL following birth, active management of the third stage may reduce the number of women with anaemia after birth (average RR 0.50, 95% CI 0.30 to 0.83, 2 studies, 1572 women; GRADE: low quality). We also found that active management of the third stage may make little or no difference to the number of babies admitted to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, 2 studies, 3207 infants; GRADE: low quality). It is uncertain whether active management of the third stage reduces the number of babies with jaundice requiring treatment (RR 0.96, 95% CI 0.55 to 1.68, 2 studies, 3142 infants, I = 66%; GRADE: very low quality). There were no data on our other primary outcomes of very severe PPH at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management reduces mean maternal blood loss at birth and probably reduces the rate of primary blood loss greater than 500 mL, and the use of therapeutic uterotonics. Active management also probably reduces the mean birthweight of the baby, reflecting the lower blood volume from interference with placental transfusion. In addition, it may reduce the need for maternal blood transfusion. However, active management may increase maternal diastolic blood pressure, vomiting after birth, afterpains, use of analgesia from birth up to discharge from the labour ward, and more women returning to hospital with bleeding (outcome not pre-specified).In the comparison of women at low risk of excessive bleeding, there were similar findings, except it was uncertain whether there was a difference identified between groups for severe primary PPH (average RR 0.31, 95% CI 0.05 to 2.17; 2 studies, 2941 women, I = 71%), maternal Hb less than 9 g/dL at 24 to 72 hours (average RR 0.17, 95% CI 0.02 to 1.47; 1 study, 193 women) or the need for neonatal admission (average RR 1.02, 95% CI 0.55 to 1.88; 1 study, 1512 women). In this group, active management may make little difference to the rate of neonatal jaundice requiring phototherapy (average RR 1.31, 95% CI 0.78 to 2.18; 1 study, 1447 women).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, for example, omitting ergot and deferring cord clamping, but we have no direct evidence of this here.
AUTHORS' CONCLUSIONS
Although the data appeared to show that active management reduced the risk of severe primary PPH greater than 1000 mL at the time of birth, we are uncertain of this finding because of the very low-quality evidence. Active management may reduce the incidence of maternal anaemia (Hb less than 9 g/dL) following birth, but harms such as postnatal hypertension, pain and return to hospital due to bleeding were identified.In women at low risk of excessive bleeding, it is uncertain whether there was a difference between active and expectant management for severe PPH or maternal Hb less than 9 g/dL (at 24 to 72 hours). Women could be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.It must be emphasised that this review includes only a small number of studies with relatively small numbers of participants, and the quality of evidence for primary outcomes is low or very low.
Topics: Birth Weight; Constriction; Delivery, Obstetric; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Labor Stage, Third; Oxytocics; Placenta; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 30754073
DOI: 10.1002/14651858.CD007412.pub5 -
Journal of Midwifery & Women's Health Jan 2019Studies have shown that women with obesity have longer labors. The purpose of this systematic review and meta-analysis is to examine existing evidence regarding labor... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Studies have shown that women with obesity have longer labors. The purpose of this systematic review and meta-analysis is to examine existing evidence regarding labor induction in women with obesity, including processes and outcomes. The primary outcome was cesarean birth following labor induction. Secondary outcomes were the timing and dosage of prostaglandins, the success of mechanical cervical ripening methods, and synthetic oxytocin dose and timing.
METHODS
Searches were performed in PubMed, MEDLINE, Embase, CINAHL, EBSCO, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Effects, Google Scholar, and ClinicalTrials.gov. Searches were limited to studies published in English after 1990. Ten studies published between 2009 and 2017 were included in this review. All were observational studies comparing processes and outcomes of induction of labor in relation to maternal body mass index. The primary outcome was cesarean birth following labor induction. We assessed heterogeneity using Cochran's Q test and tau-squared and I statistics. We also calculated fixed-effect models to estimate pooled relative risks and weighted mean differences.
RESULTS
Ten cohort studies met inclusion criteria; 8 studies had data available for a meta-analysis of the primary outcome. Cesarean birth was more common among women with obesity compared with women of normal weight following labor induction (Mantel-Haenszel fixed-effect odds ratio, 1.82; 95% CI, 1.55-2.12; P < .001). Maternal obesity was associated with a longer time to birth, higher doses of prostaglandins, less frequent success of cervical ripening methods, and higher dose of synthetic oxytocin, as well as a longer time to birth after oxytocin use.
DISCUSSION
Women with obesity are more likely than women with a normal weight to end labor induction with cesarean birth. Additionally, women with obesity require longer labor inductions involving larger, more frequent applications of both cervical ripening methods and synthetic oxytocin.
Topics: Cervical Ripening; Cesarean Section; Female; Humans; Labor, Induced; Obesity, Maternal; Observational Studies as Topic; Outcome and Process Assessment, Health Care; Oxytocics; Oxytocin; Pregnancy; Pregnancy Outcome; Prostaglandins
PubMed: 30648804
DOI: 10.1111/jmwh.12935 -
The Cochrane Database of Systematic... Dec 2018Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The current World Health Organization (WHO) recommendation for preventing PPH is 10 IU (international units) of intramuscular or intravenous oxytocin. There are several uterotonic agents for preventing PPH but there is still uncertainty about which agent is most effective with the least side effects. This is an update of a Cochrane Review which was first published in April 2018 and was updated to incorporate results from a recent large WHO trial.
OBJECTIVES
To identify the most effective uterotonic agent(s) to prevent PPH with the least side effects, and generate a ranking according to their effectiveness and side-effect profile.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (24 May 2018), and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and side effects of uterotonic agents with other uterotonic agents, placebo or no treatment for preventing PPH were eligible for inclusion. Quasi-randomised trials were excluded. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. Secondary outcomes included blood loss and related outcomes, morbidity outcomes, maternal well-being and satisfaction and side effects. Primary outcomes were also reported for pre-specified subgroups, stratifying by mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of administration. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available agents.
MAIN RESULTS
The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196).Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin.All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL.Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe morbidity as these outcomes were rare in the included randomised trials where they were reported.The two combination regimens were associated with important side effects. When compared with oxytocin, misoprostol plus oxytocin combination increases the likelihood of vomiting (RR 2.11, 95% CI 1.39 to 3.18, high certainty) and fever (RR 3.14, 95% CI 2.20 to 4.49, moderate certainty). Ergometrine plus oxytocin increases the likelihood of vomiting (RR 2.93, 95% CI 2.08 to 4.13, moderate certainty) and may make little or no difference to the risk of hypertension, however absolute effects varied considerably and the certainty of the evidence was low for this outcome.Subgroup analyses did not reveal important subgroup differences by mode of birth (caesarean versus vaginal birth), setting (hospital versus community), risk of PPH (high versus low risk for PPH), dose of misoprostol (≥ 600 mcg versus < 600 mcg) and regimen of oxytocin (bolus versus bolus plus infusion versus infusion only).
AUTHORS' CONCLUSIONS
All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.
Topics: Drug Therapy, Combination; Ergonovine; Female; Fever; Humans; Hypertension; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Prostaglandins; Randomized Controlled Trials as Topic; Vomiting
PubMed: 30569545
DOI: 10.1002/14651858.CD011689.pub3 -
The Cochrane Database of Systematic... Dec 2018The World Health Organization (WHO) guidelines for safe abortion recommend medical abortion with mifepristone and misoprostol or surgical abortion with vacuum aspiration...
BACKGROUND
The World Health Organization (WHO) guidelines for safe abortion recommend medical abortion with mifepristone and misoprostol or surgical abortion with vacuum aspiration or dilation and evacuation as safe and effective options for women. However, no specific clinical considerations are stipulated within these guidelines for women living with HIV. Concerns have been raised that women living with HIV may be at greater risk of adverse abortion outcomes compared to HIV-uninfected women due to immunosuppression, high rates of co-infection with other sexually transmitted infections, and possible contraindications between medications used for medical abortion and antiretroviral therapy regimens.
OBJECTIVES
Our primary objective was to assess the effectiveness and safety of medical versus surgical abortion among women living with HIV. Our secondary objectives were to: (1) compare outcomes of medical and surgical abortion between women living with HIV and women without HIV and (2) describe outcomes of medical and surgical abortion among women living with HIV.
SEARCH METHODS
We conducted our search on 17 April 2018. We searched for all published and unpublished trials and observational studies of medical and surgical abortion among women living with HIV. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform using a combination of terms for abortion and HIV. We searched conference websites for relevant abstracts. We also sought unpublished data stratified by HIV status that could be newly analyzed.
SELECTION CRITERIA
We considered randomized controlled trials (RCTs), non-RCTs, and observational studies. We considered: (1) studies on the effectiveness and safety of medical versus surgical abortion among women living with HIV; (2) studies comparing outcomes of abortion for both methods between women living with HIV and women without HIV; and (3) studies that described outcomes of abortion among women living with HIV.
DATA COLLECTION AND ANALYSIS
One review author screened the titles, abstracts, citation information, and descriptor terms for citations initially identified by the search. We obtained the full-text articles of all potentially eligible studies when these were available. Two review authors independently examined the full-text articles for compliance with the inclusion criteria and determination of final study selection. We planned to conduct meta-analysis if a sufficient number of studies (at least three) addressed the same research question and presented data on sufficiently comparable outcomes.
MAIN RESULTS
Of 3840 records screened, we identified just one conference abstract that met our inclusion criteria. This prospective cohort study assessed the efficacy and acceptability of home administration of misoprostol for early medical abortion among women living with HIV who were of less than 63 days amenorrhea in Ukraine. Medical abortion was effective in 65 of 68 cases (96%) examined. The small number of failures included incomplete abortion (n = 1), heavy bleeding (n = 1), and ongoing pregnancy (n = 1). There were no serious infections.
AUTHORS' CONCLUSIONS
Due to the paucity of studies, we were unable to determine if outcome differences exist between women living with HIV and women without HIV who undergo medical or surgical abortion. We found no evidence suggesting that medical or surgical abortions are unsafe for women living with HIV. While additional research would strengthen the evidence base, healthcare providers should not be deterred from providing access to safe abortion to their patients living with HIV.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Administration, Oral; Administration, Sublingual; Adult; Drug Administration Schedule; Female; HIV Long-Term Survivors; Humans; Mifepristone; Misoprostol; Prospective Studies
PubMed: 30566226
DOI: 10.1002/14651858.CD012834.pub2